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Cell Mol Life Sci . 2021 Dec 24

Activation of neutral sphingomyelinase 2 through hyperglycemia contributes to endothelial apoptosis via vesicle-bound intercellular transfer of ceramides

Andreas Zietzer, Alina Lisann Jahnel, Marko Bulic, Katharina Gutbrod, Philip Düsing, Mohammed Rabiul Hosen, Peter Dörmann, Nikos Werner, Georg Nickenig, Felix Jansen

Background: Pro-apoptotic and pro-inflammatory ceramides are crucially involved in atherosclerotic plaque development. Local cellular ceramide accumulation mediates endothelial apoptosis, especially in type 2 diabetes mellitus, which is a major cardiovascular risk factor. In recent years, large extracellular vesicles (lEVs) have been identified as an important means of intercellular communication and as regulators of cardiovascular health and disease. A potential role for lEVs as vehicles for ceramide transfer and inductors of diabetes-associated endothelial apoptosis has never been investigated.

PMID: 34951654